Clusterin - P10909 (CLUS_HUMAN)


Protein Feature View of PDB entries mapped to a UniProtKB sequence  

Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement (PubMed:2780565). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). UniProt
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Subunit Structure
Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain (PubMed:12047389, PubMed:1491011, PubMed:1551440, PubMed:2780565, PubMed:2387851, PubMed:8328966, PubMed:1974459). Self-associates and forms higher oligomers (PubMed:1903064). Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ (PubMed:17407782, PubMed:8328966, PubMed:17412999). Slightly acidic pH promotes interaction with misfolded proteins (PubMed:12176985). Forms high-molecular weight oligomers upon interaction with misfolded proteins (PubMed:19535339). Interacts with APOA1, LRP2, CLUAP1 and PON1 (PubMed:15480429, PubMed:17260971, PubMed:1742316, PubMed:8292612, PubMed:1903064). Interacts with the complement complex (PubMed:2601725). Interacts (via alpha chain) with XRCC6 (By similarity). Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes (PubMed:17451556, PubMed:20068069). Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane (PubMed:16113678). Does not interact with BAX in unstressed cells (PubMed:16113678). Found in a complex with LTF, CLU, EPPIN and SEMG1 (PubMed:17567961). Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this interaction promotes CLU stability and facilitates stress-induced CLU retrotranslocation from the secretory pathway to the mitochondria, thereby reducing stress-induced apoptosis by stabilizing mitochondrial membrane integrity (PubMed:22689054). Interacts (isoform 4) with BCL2L1; this interaction releases and activates BAX and promotes cell death (PubMed:21567405). Interacts with TGFBR2 and ACVR1 (PubMed:8555189). Interacts (secreted form) with STMN3; this interaction may act as an important modulator during neuronal differentiation (By similarity). UniProt
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